Back to resultsInduction and Maintenance of Castration After Subcutaneous Injections of Triptorelin Pamoate in Patients With Prostate Cancer (DKP 3M SC)
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Triptorelin Pamoate 11.25mg
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically proven locally advanced or metastatic prostate cancer who are suitable for androgen deprivation therapy
- Male aged ≥18 years old
- Screening testosterone level of >125 ng/dL
- Life expectancy of greater than 12 months in the judgement of the Investigator
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Willing to give signed informed consent freely
- Able to adhere to the study visit schedule and other protocol requirements.
Exclusion Criteria:
- Prior hormonal therapy for prostate cancer
- Prior surgery or radiotherapy of prostate cancer with curative intent unless disease is verified by a rising prostate specific antigen (PSA) concentration on follow up (elevated PSA values on last two tests conducted at least a month apart) and the patient is eligible for androgen deprivation therapy
- Presence or history of any other malignancy except for non melanoma skin cancer adequately treated at least 2 years before study entry
- Painful local bone lesions or spinal lesions which may lead to compression
- History of myocardial infarction, percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass graft, Class III/IV congestive heart failure, cerebrovascular accident, transient ischaemic attack, or limb claudication at rest, within six months prior to start of study treatment and ongoing symptomatic dysrhythmias, unstable angina, uncontrolled hypertension, and untreated atrial or uncontrolled ventricular arrhythmias
- Any condition in opinion of the Investigator, including other active or latent infections, medical or psychiatric conditions, or the presence of laboratory abnormalities, which could confound the ability to interpret data from the study, compromises the objective of the study or places the patient at unacceptable risk if he participates in the study
Abnormal haematological, hepatic or renal functions:
- Haemoglobin <9 g/dL, absolute neutrophil count ≤1.5 x 10^9/L or platelets ≤100 x 10^9/L
- Serum creatinine ≥1.5 times the upper limit of normal (ULN)
- Aspartate aminotransferase or alanine aminotransferase >2.5 times the ULN
- Known hypersensitivity to the study treatment, to any of its excipients
- Known active use of recreational drug or alcohol dependence in the opinion of the Investigator
- Any current use or use within six months prior to start of treatment, of medications which are known to affect the metabolism and/or secretion of androgenic hormones: e.g. ketoconazole, aminoglutethimide, oestrogens, and progesterone
- Use of systemic corticosteroids (inhaled corticosteroids and topical application of corticosteroids are permitted)
- Aged ≥90 years for the main study and ≥80 years for those included in the pharmacokinetic (PK) patient population
- Participation in any other study or receipt of any investigational compound in the 30 days (or five times the elimination half life if this is longer) prior to study entry
- Any skin or other condition that may preclude s.c. injection administration
- Known brain or epidural metastases.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
11.25mg
Arm Description
11.25mg, SC on Day 1 and Day 92
Outcomes
Primary Outcome Measures
Percentage of Subjects Demonstrating Castration at Day 29 and Maintaining Castration at Day 183
Percentage of subjects castrated (i.e. with serum testosterone <50 ng/dL or 1.735 nmol/L, using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and the proportion with castration maintained at Day 183 (after receiving 2 S.C. administrations of triptorelin pamoate, three months apart); they were calculated along with their respective 95% confidence intervals (CI) using exact methods on the ITT population at Day 29 and on the initially castrated (IC) population at Day 183
Secondary Outcome Measures
Percentage of Subjects Demonstrating Castration Before Administration of the Second Dose
Percentage of subjects demonstrating castration at Day 92 (before administration of the second dose) were also assessed using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and summarised using descriptive statistics on the ITT and IC populations.
Probability of Testosterone <50 ng/dL
Probability of testosterone <50 ng/dL from Day 29 to Day 183 was assessed as a secondary endpoint using the time to event from first administration date to first observed (and subsequently confirmed if assessment not performed at end of study or early withdrawal visits) serum testosterone level ≥50 ng/dL or ≥1.735 nmol/L at or after Day 29, assessed using the LC-MS/MS Method and Missing Data imputed by immunoassay method Kaplan-Meier Analysis.
LC-MS/MS: Liquid Chromatography-Tandem Mass Spectrometry
Percentage of Subjects Demonstrating Castration With Testosterone Level <50 ng/dL at Day 95
Percentage of subjects demonstrating castration at Day 95 (3-4 days after administration of the second dose to assess the suppression of acute-on-chronic effect following the second administration) were also assessed using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and summarised using descriptive statistics on the ITT and IC populations.
Time to Achieve Castration (Tcast)
Time to castration (Tcast) from first administration date until first observed serum testosterone level <50 ng/dL or <1.735 nmol/L evaluated using the immunoassay method only (i.e. defined as the number of days between the injection time at Day 1 and castration achievement)
Plasma Triptorelin Levels (Cmin)
Minimal triptorelin plasma concentration at the end of each dosage interval just before the next dose injection (Cmin) for Days 92 and 183 were assessed.
Percentage Change in Prostate Specific Antigen (PSA) Levels From Baseline in All Subjects
Serum PSA level was presented throughout the study using descriptive statistics displaying raw values, change from Baseline and percentage change from Baseline at each visit in all subjects from the ITT population only. Additionally, the PSA level was described in subjects with elevated PSA levels (i.e. >4 ng/mL) at study entry, and the proportion of subjects with normal PSA levels (i.e. [0-4] ng/mL) at Day 183 compared to Baseline was presented.
Percentage of Subjects With Normal and Abnormal PSA Levels at Day 183 (End of Study Visit)
0-4 ng/mL (normal PSA value)
>4 ng/mL (abnormal PSA levels)
Clinically Apparent Tumor Progression
Tumour progression was recorded according to the Investigator's clinical judgement, considering the PSA levels and any other indications of disease; the clinical confirmation might be supplemented by radiological or other investigations or scans if required. The lack of clinically apparent tumour progression was assessed at Day 92 (prior to administration of the second dose) and Day 183 (end of study visit).
Percentage of Subjects With Adverse Events
Time to Cmax (Tmax) of Triptorelin
Peak Plasma Concentration Value (Cmax) of Triptorelin
Area Under the Concentration Versus Time Curve Between 0 and 24 Hours (AUC0-24) of Triptorelin
Cmin of Triptorelin in Subset of 18 Subjects
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01715129
Brief Title
Induction and Maintenance of Castration After Subcutaneous Injections of Triptorelin Pamoate in Patients With Prostate Cancer
Acronym
DKP 3M SC
Official Title
A Phase III Single Arm Study to Evaluate the Efficacy, Safety and Local Tolerability of a Subcutaneous 3-month Formulation of Triptorelin Pamoate (11.25 mg) in Patients With Locally Advanced or Metastatic Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
October 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ipsen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Assess the efficacy and safety of Triptorelin pamoate 3M formulation (11.25mg) when administered by subcutaneous route.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
126 (Actual)
8. Arms, Groups, and Interventions
Arm Title
11.25mg
Arm Type
Experimental
Arm Description
11.25mg, SC on Day 1 and Day 92
Intervention Type
Drug
Intervention Name(s)
Triptorelin Pamoate 11.25mg
Primary Outcome Measure Information:
Title
Percentage of Subjects Demonstrating Castration at Day 29 and Maintaining Castration at Day 183
Description
Percentage of subjects castrated (i.e. with serum testosterone <50 ng/dL or 1.735 nmol/L, using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and the proportion with castration maintained at Day 183 (after receiving 2 S.C. administrations of triptorelin pamoate, three months apart); they were calculated along with their respective 95% confidence intervals (CI) using exact methods on the ITT population at Day 29 and on the initially castrated (IC) population at Day 183
Time Frame
At Day 29 and 183
Secondary Outcome Measure Information:
Title
Percentage of Subjects Demonstrating Castration Before Administration of the Second Dose
Description
Percentage of subjects demonstrating castration at Day 92 (before administration of the second dose) were also assessed using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and summarised using descriptive statistics on the ITT and IC populations.
Time Frame
At Day 92
Title
Probability of Testosterone <50 ng/dL
Description
Probability of testosterone <50 ng/dL from Day 29 to Day 183 was assessed as a secondary endpoint using the time to event from first administration date to first observed (and subsequently confirmed if assessment not performed at end of study or early withdrawal visits) serum testosterone level ≥50 ng/dL or ≥1.735 nmol/L at or after Day 29, assessed using the LC-MS/MS Method and Missing Data imputed by immunoassay method Kaplan-Meier Analysis.
LC-MS/MS: Liquid Chromatography-Tandem Mass Spectrometry
Time Frame
Day 29 through Day 183
Title
Percentage of Subjects Demonstrating Castration With Testosterone Level <50 ng/dL at Day 95
Description
Percentage of subjects demonstrating castration at Day 95 (3-4 days after administration of the second dose to assess the suppression of acute-on-chronic effect following the second administration) were also assessed using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and summarised using descriptive statistics on the ITT and IC populations.
Time Frame
Day 95
Title
Time to Achieve Castration (Tcast)
Description
Time to castration (Tcast) from first administration date until first observed serum testosterone level <50 ng/dL or <1.735 nmol/L evaluated using the immunoassay method only (i.e. defined as the number of days between the injection time at Day 1 and castration achievement)
Time Frame
Up to Day 36
Title
Plasma Triptorelin Levels (Cmin)
Description
Minimal triptorelin plasma concentration at the end of each dosage interval just before the next dose injection (Cmin) for Days 92 and 183 were assessed.
Time Frame
At Day 92 and 183
Title
Percentage Change in Prostate Specific Antigen (PSA) Levels From Baseline in All Subjects
Description
Serum PSA level was presented throughout the study using descriptive statistics displaying raw values, change from Baseline and percentage change from Baseline at each visit in all subjects from the ITT population only. Additionally, the PSA level was described in subjects with elevated PSA levels (i.e. >4 ng/mL) at study entry, and the proportion of subjects with normal PSA levels (i.e. [0-4] ng/mL) at Day 183 compared to Baseline was presented.
Time Frame
From Day 1 (Baseline) to Day 183 (End of study)
Title
Percentage of Subjects With Normal and Abnormal PSA Levels at Day 183 (End of Study Visit)
Description
0-4 ng/mL (normal PSA value)
>4 ng/mL (abnormal PSA levels)
Time Frame
At Day 183
Title
Clinically Apparent Tumor Progression
Description
Tumour progression was recorded according to the Investigator's clinical judgement, considering the PSA levels and any other indications of disease; the clinical confirmation might be supplemented by radiological or other investigations or scans if required. The lack of clinically apparent tumour progression was assessed at Day 92 (prior to administration of the second dose) and Day 183 (end of study visit).
Time Frame
Day 92 and 183
Title
Percentage of Subjects With Adverse Events
Time Frame
Up to Day 183
Title
Time to Cmax (Tmax) of Triptorelin
Time Frame
At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1
Title
Peak Plasma Concentration Value (Cmax) of Triptorelin
Time Frame
At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1
Title
Area Under the Concentration Versus Time Curve Between 0 and 24 Hours (AUC0-24) of Triptorelin
Time Frame
At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1
Title
Cmin of Triptorelin in Subset of 18 Subjects
Time Frame
At Day 92 and 183
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically proven locally advanced or metastatic prostate cancer who are suitable for androgen deprivation therapy
Male aged ≥18 years old
Screening testosterone level of >125 ng/dL
Life expectancy of greater than 12 months in the judgement of the Investigator
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Willing to give signed informed consent freely
Able to adhere to the study visit schedule and other protocol requirements.
Exclusion Criteria:
Prior hormonal therapy for prostate cancer
Prior surgery or radiotherapy of prostate cancer with curative intent unless disease is verified by a rising prostate specific antigen (PSA) concentration on follow up (elevated PSA values on last two tests conducted at least a month apart) and the patient is eligible for androgen deprivation therapy
Presence or history of any other malignancy except for non melanoma skin cancer adequately treated at least 2 years before study entry
Painful local bone lesions or spinal lesions which may lead to compression
History of myocardial infarction, percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass graft, Class III/IV congestive heart failure, cerebrovascular accident, transient ischaemic attack, or limb claudication at rest, within six months prior to start of study treatment and ongoing symptomatic dysrhythmias, unstable angina, uncontrolled hypertension, and untreated atrial or uncontrolled ventricular arrhythmias
Any condition in opinion of the Investigator, including other active or latent infections, medical or psychiatric conditions, or the presence of laboratory abnormalities, which could confound the ability to interpret data from the study, compromises the objective of the study or places the patient at unacceptable risk if he participates in the study
Abnormal haematological, hepatic or renal functions:
Haemoglobin <9 g/dL, absolute neutrophil count ≤1.5 x 10^9/L or platelets ≤100 x 10^9/L
Serum creatinine ≥1.5 times the upper limit of normal (ULN)
Aspartate aminotransferase or alanine aminotransferase >2.5 times the ULN
Known hypersensitivity to the study treatment, to any of its excipients
Known active use of recreational drug or alcohol dependence in the opinion of the Investigator
Any current use or use within six months prior to start of treatment, of medications which are known to affect the metabolism and/or secretion of androgenic hormones: e.g. ketoconazole, aminoglutethimide, oestrogens, and progesterone
Use of systemic corticosteroids (inhaled corticosteroids and topical application of corticosteroids are permitted)
Aged ≥90 years for the main study and ≥80 years for those included in the pharmacokinetic (PK) patient population
Participation in any other study or receipt of any investigational compound in the 30 days (or five times the elimination half life if this is longer) prior to study entry
Any skin or other condition that may preclude s.c. injection administration
Known brain or epidural metastases.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director, Uro-Oncology
Organizational Affiliation
Ipsen
Official's Role
Study Director
Facility Information:
City
Pleven
Country
Bulgaria
City
Plovdiv
Country
Bulgaria
City
Shumen
Country
Bulgaria
City
Varna
Country
Bulgaria
City
Suresnes
Country
France
City
Daugavpils
Country
Latvia
City
Riga
Country
Latvia
City
Kutno
Country
Poland
City
Warsaw
Country
Poland
City
Wroclaw
Country
Poland
City
Bucharest
Country
Romania
City
Craiova
Country
Romania
12. IPD Sharing Statement
Learn more about this trial
Induction and Maintenance of Castration After Subcutaneous Injections of Triptorelin Pamoate in Patients With Prostate Cancer
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